D-pantothenic acid is useful as vitamin. Prior art processes for producing D-pantothenic acid include (1) a process which comprises optically resolving DL-pantolactone and chemically condensing the resulting D-pantolactone with .beta.-alanine or a salt thereof in methanol, (2) a process which comprises hydrolyzing a D-pantothenic acid ester with a microorganism or enzyme to obtain D-pantothenic acid, or selectively hydrolyzing only D-isomer of a DL-pantothenic acid ester to obtain D-pantothenic acid (JP-A 1-228487, JP-A 1-228488), (3) a process which comprises contacting potassium D-pantoate, .beta.-alanine and ATP with resting cells of a microorganism or an enzyme thereof in tris buffer (Journal of Biological Chemistry, Vol. 198, p.23 (1952), Abstracts of Papers 176th American Chemical Society National Meeting, Division of Microbial and Biochemical Technology, Vol. 48 (1978), etc.), (4) a process which comprises culturing a particular microorganism in the presence of DL-pantoic acid and .beta.-alanine and specifically condensing D-pantoic acid with .beta.-alanine to obtain D-pantothenic acid (JP-A 5-23191), and (5) a process which comprises culturing a particular microorganism in the presence of .beta.-alanine to obtain D-pantothenic acid (JP-A 6-261772).
Processes for producing D-pantoic acid and/or D-pantolactone include (6) a process which comprises optically resolving chemically synthesized DL-pantolactone with a resolving agent such as quinine and brucine, (7) a process which comprises decomposing only L-pantolactone in DL-pantolactone with a particular microorganism to obtain only D-pantolactone, (8) a process which comprises oxidizing only L-pantolactone in DL-pantolactone with a particular microorganism to obtain ketopantolactone, which is then asymmetrically reduced to D-pantolactone (JP-A 47-19745), (9) a process which comprises asymmetrically reducing chemically synthesized ketopantolactone with a particular microorganism to obtain D-pantolactone (JP-B 61-14797), (10) a process which comprises selectively and asymmetrically hydrolyzing L-pantolactone in DL-pantolactone with a particular microorganism to obtain D-pantolactone (JP-A 57-152895 and JP-A 62-294092), (11) a process which comprises selectively and asymmetrically hydrolyzing D-pantolactone in DL-pantolactone with a particular microorganism to obtain D-pantoic acid (JP-B 3-65198), and (12) a process which comprises culturing a particular microorganism to biosynthesize D-pantoic acid from glucose (JP-A 6-261772).
In industrial production of D-pantothenic acid (hereinafter including a salt thereof), above process (1) not only requires complicated steps to synthesize the main raw material DL-pantolactone, but also contains complicated and difficult optical resolution steps. Above process (2) disadvantageously needs a step for producing a D-pantothenic acid ester or DL-pantothenic acid ester from DL-pantolactone. Above process (3) disadvantageously uses expensive ATP and tris buffer, and it is an impractical process because it produces only a trace amount of pantothenic acid from the expensive starting material D-pantoic acid. Above process (4) is simpler than the other processes, but it requires steps for producing DL-pantoic acid and racemization. Above process (5) is more simplified than above process (4). However, the activity of the valine biosynthesis pathway located at the upstream of the pantothenic acid biosynthesis pathway disappears at the late stage of the culture, and the pantothenic acid production stops with depletion of valine. The production is thus limited.
Most of the processes for producing D-pantoic acid and/or D-pantolactone disadvantageously use the starting material DL-pantolactone that must be synthesized through complicated steps. In addition, above process (6) disadvantageously uses an expensive resolving agent and has difficulty in recovering D-pantolactone. Above process (7) is disadvantageous because half of the DL-pantolactone is lost. Above processes (8), (9), (10) and (11) have great difficulty in producing only D-isomer in 100% optical yield in the culture solution because of the characteristics of the microorganism to be used and the characteristics of pantolactone or pantoic acid. Furthermore, above processes (6), (10) and (11) requires additional complicated steps to recover and recycle the remaining L-isomer. The D-pantoic acid production in above process (12) depends on the activity of valine biosynthesis as in above pantothenic acid production process (5).